Subscribe to RSS
DOI: 10.1055/s-0033-1363220
Quantitative Determination of Myricetin in Rat Plasma by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry and its Absolute Bioavailability
Publication History
received 29 September 2013
accepted 25 November 2013
Publication Date:
19 December 2013 (online)
![](https://www.thieme-connect.de/media/drugres/201410/lookinside/thumbnails/10.1055-s-0033-1363220-1.jpg)
Abstract
Myricetin is a widely distributed bioactive flavonoid with scientific interest attributed to its anti-oxidant, antitumor, and anti-inflammatory properties. A specific and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated for identification and quantification of myricetin in rat plasma after oral and intravenous administrations. Kaempferol was used as an internal standard. Followed by β-glucuronidase and sulfatase hydrolysis and liquid-liquid extraction with ethyl acetate, the analytes were separated on an Acquity UPLC BEH C18 column (2.1×50 mm, 1.7 μm) and analyzed in the selected ion recording with a negative electrospray ionization mode. The developed method was validated for selectivity, accuracy, precision, linearity, recovery, stability and matrix effect. The assay was validated over a wide concentration range of 2–4 000 ng/mL. Intra- and inter-day precisions were all less than 13.49% and accuracy ranged from 95.75 to 109.80%. The present method was successfully applied to investigate a pharmacokinetic study of myricetin following intravenous and oral administrations to rats. The absolute bioavailability was found to be 9.62% and 9.74% at 2 oral doses (50 mg/kg and 100 mg/kg, respectively), which indicated myricetin was poorly absorbed after oral administration. To our knowledge, this is the first pharmacokinetic evaluation of myricetin as a single active pharmaceutical ingredient in preclinical studies.
-
References
- 1 Wang SJ, Tong Y, Lu S et al. Anti-inflammatory activity of myricetin isolated from Myrica rubra Sieb. Et Zucc leaves. Planta Med 2010; 76: 1492-1496
- 2 Tiwari R, Mohan M, Kastur S et al. Cardioprotective potential of myricetin in isoproterenol-induced myocardial infarction in Wistar rats. Phytother Res 2009; 23: 1361-1366
- 3 Gao H, Kuroyanagi M, Wu L et al. Antitumor-promoting constituents from Dioscorea bulbifera L. in JB6 mouse epidermal cells. Biol Pharm Bull 2002; 25: 1241-1243
- 4 Sahreen S, Khan MR, Khan RA. Hepatoprotective effects of methanol extract of Carissa opaca leaves on CCl4-induced damage in rat. BMC Complement Altern Med 2011; 11: 48
- 5 Sumino M, Sekine T, Ruangrungsi N et al. Ardisiphenols and other antioxidant principles from the fruits of Ardisia colorata. Chem Pharm Bull 2002; 50: 1484-1487
- 6 Jeong CH, Choi GN, Kim JH et al. Protective effects of aqueous extract from Cudrania tricuspidata on oxidative stress-induced neurotoxicity. Food Sci Biotechnol 2010; 19: 1113-1137
- 7 Hakkinen SH, Karenlampi SO, Heinonen IM et al. Content of the flavonols quercetin, myricetin, and kaempferol in 25 edible berries. J Agric Food Chem 1999; 47: 2274-2279
- 8 German JB, Walzem RL. The health benefits of wine. Annu Rev Nutr 2000; 20: 561-593
- 9 Wang L, Lee IM, Zhang SM et al. Dietary intake of selected flavonols, flavones, and flavonoid-rich foods and risk of cancer in middle-aged and older women. Am J Clin Nutr 2009; 89: 905-912
- 10 Gordon MH, Roedig-Penman A. Antioxidant activity of quercetin and myricetin in liposomes. Chem Phys Lipids 1998; 97: 79-85
- 11 Mahjoub MA, Ammar S, Edziri H et al. Anti-inflammatory and antioxidant activities of some extracts and pure natural products isolated from Rhus tripartitum (Ucria). Med Chem Res 2010; 19: 271-282
- 12 Phillips PA, Sangwan V, Borja-Cacho D et al. Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Cancer Lett 2011; 308: 181-188
- 13 Naz S, Siddiqi R, Ahmad S et al. Antibacterial activity directed isolation of compounds from Punica granatum. J Food Sci 2007; 72: M341-345
- 14 Scarabelli TM, Mariotto S, Abdel-Azeim S et al. Targeting STAT1 by myricetin and delphinidin provides efficient protection of the heart from ischemia/reperfusion-induced injury. FEBS Lett 2009; 583: 531-541
- 15 Zern TL, Wood RJ, Greene C et al. Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress. J Nutr 2005; 135: 1911-1917
- 16 Panickar KS, Anderson RA. Mechanisms underlying the protective effects of myricetin and quercetin following oxygen-glucose deprivation-induced cell swelling and the reduction in glutamate uptake in glial cells. Neuroscience 2011; 183: 1-14
- 17 Liu IM, Tzeng TF, Liou SS et al. Myricetin, a naturally occurring flavonol, ameliorats insulin resistance induced by a high-fructose diet in rats. Life Sci 2007; 81: 1479-1488
- 18 Delgado ME, Haza AI, Garcia A et al. Myricetin, quercetin, (+)-catechin and (-)-epicatechin protect against N-nitrosamines-induced DNA damage in human hepatoma cells. Toxicol In Vitro 2009; 23: 1292-1297
- 19 Du FY, Xiao XH, Li GK. Ionic liquid aqueous solvent-based microwave-assisted hydrolysis for the extraction and HPLC determination of myricetin and quercetin from Myrica rubra leaves. Biomed Chromatogr 2011; 25: 472-478
- 20 Beevi SS, Narasu ML, Gowda BB. Polyphenolics profile, antioxidant and radical scavenging activity of leaves and stem of Raphanus sativus L. Plant Foods Hum Nutr 2010; 65: 8-17
- 21 Zhang YS, Zhang QY, Li LY et al. Simultaneous determination and pharmacokinetic studies of dihydromyricetin and myricetin in rat plasma by HPLC-DAD after oral administration of Ampelopsis grossedentata decotion. J Chromatogr B 2007; 860: 4-9
- 22 Biesaga M. Influence of extraction methods on stability of flavonoids. J Chromatogr A 2011; 1218: 2505-2512
- 23 Lin Y, Wu B, Li Z et al. Metabolite identification of myricetin in rats using HPLC coupled with ESI-MS. Chromatographia 2012; 75: 655-660
- 24 Guo J, Xue C, Duan J et al. Fast characterization of constituents in HuangKui capsules using UPLC-QTOF-MS with collision energy and mass fragment software. Chromatographia 2011; 73: 447-456
- 25 U.S. Food and Drug Administration . FDA Guidance for industry: Bioanalytical Method Validation. U.S. Department of Health and Human Services, Food and Drug Administration. Center for Drug Evaluation and Research: Rockville 2001;
- 26 Zhao Y, Wang L, Bao Y et al. A sensitive method for the detection and quantification of ginkgo flavonols from plasma. Rapid Commun Mass Spectrom 2007; 21: 971-981
- 27 Walle T, Otake Y, Walle UK et al. Quercetin glucosides are completely hydrolyzed in ileostomy patients before absorption. J Nutr 2000; 130: 2658-2661
- 28 Shia CS, Tsai SY, Lin JC et al. Steady-state pharmacokinetics and tissue distribution of anthraquinones of Rhei Rhizoma in rats. J Ethnopharmacol 2011; 137: 1388-1394
- 29 Shia CS, Hou YC, Juang SH et al. Metabolism and pharmacokinetics of san-huang-xie-xin-tang, a polyphenol-rich chinese medicine formula, in rats and ex-vivo antioxidant activity. Evid Based Complement Alternat Med 2011; 721293
- 30 Ding Y, Peng M, Zhang T et al. Quantification of conjugated metabolites of drugs in biological matrices after the hydrolysis with β-glucuronidase and sufatase: a review of bio-analytical methods. Biomed Chromatogr 2013; 27: 1280-1295
- 31 Barve A, Chen C, Hebbar V et al. Metabolism, oral bioavailability and pharmacokinetics of chemopreventive kaempferol in rats. Biopharm Drug Dispos 2009; 30: 356-365
- 32 Li GW, Zeng XL, Xie Y et al. Pharmacokinetic properties of isorhamnetin, kaempferol and quercetin after oral gavage of total flavones of Hippophae rhamnoides L. in rats using a UPLC-MS method. Fitoterapia 2012; 83: 182-191